The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected,BCG-vaccinated adults with CD4+ T cell counts >350 cells/mm3 |
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| Institution: | 1. Aurum Institute, Johannesburg, South Africa;2. School of Public Health, University of Witwatersrand, Johannesburg, South Africa;3. Aeras, Rockville, MD, United States;4. Crucell Holland N.V., Leiden, The Netherlands;1. HealthCore, Inc., 800 Delaware Avenue, Fifth Floor, Wilmington, DE 19801, United States;2. Department of Epidemiology, Merck Research Laboratories, 351 N. Sumneytown Pike, North Wales, PA 19454, United States;1. Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland;2. Nationales Zentrum für Mykobakterien, Gloriastrasse 30/32, 8006 Zurich, Switzerland;3. Microbiology Services, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom;4. Unitat de Tuberculosi Experimental, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, CIBERES, Badalona, Catalonia, Spain;5. Deptartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;6. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland;1. Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA;2. Elsa Biologics, LLC, Box 25725, WA 98165, USA;1. Pediatrics, Rathausgasse 1, 79336 Herbolzheim, Germany;2. ASP 7 Ragusa, Dipartimento di Prevenzione, servizio di Epidemiologia e Prevenzione, Via Aldo Licitra 11, 97100, Ragusa, Italy;3. Sanofi Pasteur MSD, 162 Avenue Jean Jaurès, CS 50712, 69367 Lyon Cedex 07, France;1. Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;2. Vaccination and Immunotherapy Centre, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;3. Department of Microbiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;4. Clinical Research Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;5. Service de Médecine du Personnel, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;6. Biofabri, Porriño, Spain;7. Department of Microbiology, Faculty of Medicine, University of Zaragoza, Spain;8. CIBERES and Research Network on Respiratory Diseases, Spanish Ministry of Health and Instituto de Salud Carlos III, Madrid, Spain;9. Servicio de Microbiología, Hospital Miguel Servet, ISS Aragón, Zaragoza, Spain |
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| Abstract: | BackgroundThe safety and immunogenicity of a replication deficient adenovirus serotype 35 tuberculosis (TB) vaccine containing gene inserts for Antigens (Ag) 85A, Ag85B and TB10.4 (AERAS-402/AD35.TB-S) was evaluated in previously BCG vaccinated, HIV-infected South African adults with baseline CD4 counts >350 cells/mm3.MethodsSubjects were randomized (1:1) to receive two doses of either intramuscular AERAS-402/AD35.TB-S or placebo at month 0 and at month 1. Participants were monitored for adverse events 28 days after each vaccination and for serious adverse events over 12 months. CD4+ and CD8+ T-cell and antibody responses to vaccine antigens were evaluated post first and second vaccination.Results26 subjects were randomly assigned to receive AERAS-402/AD35.TB-S (N = 13) or placebo (N = 13). The mean age was 29.0 years, all were Black-African, 88.5% were female, 46.2% were QuantiFERON Test (QFT) positive at baseline, and the median CD4 count was 559.5 cells/mm3, all similar by treatment group. All subjects received their first vaccination and 24 subjects received their second vaccination. Injection site reactions and some systemic reactions were reported more commonly in the AERAS-402/AD35.TB-S versus placebo recipients. AERAS-402/AD35.TB-S did not appear to influence CD4 counts and HIV-1 viral load over the course of study follow-up. AERAS-402/AD35.TB-S induced a mixed CD4+ T-cell and CD8+ T-cell responses to Ag85B. The CD4+ T-cell responses peaked to Ag85A and Ag85B 14 days after the second vaccination and had declined by Day 182. AERAS-402/AD35.TB-S predominantly induced CD4+ T-cells expressing three (IFN-γ, TNF, IL-2) or two (IL-2 and TNF) cytokines, two weeks after the last vaccination, which did not differ by baseline Quantiferon test status. AERAS-402/AD35.TB-S induced strong Ag85A and Ag85B specific antibody responses, particularly after the second vaccination.ConclusionAERAS-402/AD35.TB-S was well tolerated, safe and induced predominantly polyfunctional CD4+ and CD8+ T-cell responses to vaccine. |
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| Keywords: | Tuberculosis HIV Vaccines Safety Immunogenicity DOH-27-0809-2497 Clinicaltrials gov (NHREC no NCT01017536) |
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